Neuropsychological testing has revealed that affectively ill patients have impaired performance on tests involving implicit memory (priming), the Halstead Category Test, and recognition of facial emotional expression in contrast with unimpaired verbal emotion recognition tasks. The neural substrates of these deficits are systematically being explored by a variety of techniques including testing patients utilizing O(15) blood blow studies with PET methodology. CAT scan studies have revealed increased VBR in patients with affective disorders unrelated to the course of illness, but positively related to age, measures of cortisol hypersecretion, and impairment on the Halstead Category Test. MRI studies suggest decreased area and volume of the temporal lobe in affectively ill subjects compared with controls. Evidence of frontal hypometabolism is revealed on PET scan studies in patients with primary affective disorders as well as depression associated with epilepsy. Temporal and parietal alterations are also evident. Procaine-activation studies reveal marked alterations in psychosensory symptoms with a range of affective changes. Bipolar patients appear particularly prone to euphoric responses, while dysphoric responses occur in relationship to degree of fast activation in the EEG of temporal lobe structures. O(15) PET procedures have been conducted in patients and normal volunteers and reveal procaine-induced increases in blood flow in anterior temporal lobe and/or basal frontal areas as well as in cingulate gyrus. Procaine tests will be continued in patients on and off carbamazepine as well as in cocaine abusers with and without histories of panic attacks.